A systematic study to evaluate the safety of ticagrelor combined with aspirin in the treatment of PCI patients in Chinese population: A single nucleotide polymorphisms study

• Published in: Drug metabolism and pharmacokinetics Vol. 53; p. 100468
• Main Authors: Zheng, ShaoJun, Xu, YiFan, Jie, Qiong, Mu, HuiWen, Zhang, Xing, Zhu, JianCheng, Zhu, YuBing, Chen, XiJing, Chen, ShaoLiang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2023
• Subjects: Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - genetics; Aspirin - adverse effects; China; Cytochrome P-450 CYP3A - genetics; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention - adverse effects; Platelet Aggregation Inhibitors - adverse effects; Polymorphism, Single Nucleotide - genetics; Receptors, Cell Surface; Single nucleotide polymorphism; Steady-state trough concentration; Ticagrelor; Ticagrelor - adverse effects; Treatment Outcome; China; Ticagrelor; Steady-state trough concentration; Single nucleotide polymorphism
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2022.100468

The aim of this study was to identify genes and their associated loci related to ticagrelor pharmacokinetics and pharmacodynamics in Chinese patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). The study included 1115 patients with ACS who received a drug-eluting stent implantation between October 2019 and January 2021. Among them, 98 cases of adverse reactions were observed; thus, 97 cases without adverse reactions were selected as the comparison group. The steady-state serum drug concentration was determined via high-performance liquid chromatography-mass spectrometry, and 15 single nucleotide polymorphism (SNP) loci were genotyped using the SNaPshot SNP Multiplex System. Our results showed that age and sex may affect ticagrelor serum concentration in patients with ACS. In particular, the SNPs CYP3A4*1 (rs2242480 C > T), IGT2B (rs5911 A > C), P2Y12 (rs6787801) and CYP3A5 (rs776746 C > T) may affect the steady-state blood concentration of ticagrelor after PCI in ACS patients, and CYP3A4*1 may also be related to adverse events. In addition, we found that the SNPs PEAR1 (rs4661012 T > G) and P2Y12 (rs6787801 A > G) may be associated with dyspnea. These findings can provide a useful reference to establish guidelines for future clinical individualized dosage regimens of ticagrelor after PCI. [Display omitted]